Although very significant advances have been made in recent years in the treatment of heart disease, diseases of cardiovascular origin still remain the number one killer.
In order to develop effective modes of treatment, one must first understand the cause(s) and mechanisms underlying the disease process. This understanding requires investigative research which in turn requires suitable models that closely mimic the pathophysiology of the disease. These models can be employed to perform experiments to learn the basic mechanisms underlying disease and/or for testing procedures or agents suspected to offer some protection or which may reduce the harmful effects of the disease.
As is of course well recognized, occlusive artery disease and/or intracoronary thrombosis can cause a heart attack by critically reducing the blood supply to the heart muscle (ischemia). If blood flow is not resupplied within a reasonable time, the ischemic tissue is irreversibly injured.
To reperfuse ischemic tissue, physicians may elect to bypass the narrowed vessels or to restore blood flow using angioplasty (balloon procedure) or thrombolysis (dissolve clot). The choice of which procedure to use depends on the nature and severity of the coronary compromise.
In the last few years, it has become clear that early in reperfusion there is a modest extension of damage to the heart. This extension is clearly much less than that which would occur if reperfusion did not take place. Nevertheless, the extension of heart disease is very real and is recognized to the extent that it has become known in the art as "reperfusion injury."
Evidence reported in the literature suggests that activated blood cells play an important role in reperfusion injury. Consequently, researchers in a number of academic and industrial laboratories have been attempting to learn more about how the injury occurs and how to prevent it. Additionally, pharmaceutical companies have exhibited keen interest in the development of an adjunct reagent to accompany thrombolysis treatment to minimize reperfusion injury.
The development of any such adjunct reagent involves several steps including initially testing the pharmaceutical in an appropriate animal model prior to obtaining FDA approval for any clinical studies in humans. The desirable characteristics for an animal model include: (1) it should mimic the pathophysiologic process; (2) it should demonstrate consistent, measurable pathophysiologic effects; and (3) it should be easy to learn, straightforward to apply, not be labor-intensive, and be reasonably inexpensive. Current models do not possess all the desirable characteristics enumerated above for routine use as test systems.
A primary object of this invention, therefore, is to provide a novel test procedure which satisfies the above-mentioned requirements and is accordingly quite suitable for routine evaluation and screening of cardioprotective reagents.
Another object is to provide a test procedure which can clearly demonstrate in a straightforward manner the contribution of blood components to ischemia-reperfusion injury.
A further object is to provide a simple, reliable, cost-efficient experimental model of myocardial ischemia-reperfusion injury that accounts for the contribution of blood components to the compromise of cardiac function.
Still another object is to devise a test procedure and method of the foregoing description which utilizes small laboratory mammals rather than canines or other larger animals.